1. Field of the Invention
This invention relates to a fluorescence detecting apparatus suitable for use in a fluorescence diagnosing system, wherein a diagnosis of a tumor is carried out by irradiating excitation light to a region of interest in a living body, to which a photosensitive substance, that has a strong affinity for the tumor and is capable of producing fluorescence when it is excited with the excitation light, has been administered, and detecting the intensity of fluorescence, which is produced by the photosensitive substance and an intrinsic dye in the living body when the region of interest in the living body is exposed to the excitation light, or wherein a diagnosis of a tumor is carried out by irradiating excitation light to a region of interest in a living body, to which no photosensitive substance has been administered, and detecting the intensity of intrinsic fluorescence, which is produced by an intrinsic dye in the living body when the region of interest in the living body is exposed to the excitation light.
2. Description of the Prior Art
Extensive research has heretofore been conducted on the so-called photodynamic diagnosis (PDD) technique. With the PDD technique, a photosensitive substance (such as ATX-S10, 5-ALA, NPe6, HAT-D01 or Photofrin-2), which has an affinity for a tumor and is capable of producing fluorescence when it is excited with light, is employed as a fluorescent diagnosis drug. The photosensitive substance is administered to a living body and is absorbed by a tumor part, such as a cancer, of the living body. Excitation light, which has wavelengths falling within the excitation wavelength range for the photosensitive substance, is then irradiated to the region containing the tumor part, and fluorescence is thereby produced from the fluorescent diagnosis drug having been accumulated at the tumor part. By the detection of the fluorescence, the location and infiltration range of the diseased part is displayed as an image, and the displayed image is used in making a diagnosis of the tumor part.
Fluorescence diagnosing systems for carrying out the PDD technique have been disclosed in, for example, U.S. Pat. No. 4,556,057, and Japanese Unexamined Patent Publication Nos. 1(1989)-136630 and 7(1995)-59783. Basically, the disclosed fluorescence diagnosing systems comprise an excitation light irradiating means for irradiating excitation light, which has wavelengths falling within the excitation wavelength range for a photosensitive substance, to a living body, an imaging means for detecting the fluorescence produced by the photosensitive substance and forming a fluorescence image of the living body, and an image displaying means for receiving the output from the imaging means and displaying the fluorescence image. In many cases, the fluorescence diagnosing systems take on the form built in endoscopes, which are inserted into the body cavities, operating microscopes, or the like.
Techniques for making a diagnosis of a tumor part without a photosensitive substance being administered to the living body have also been proposed. With the proposed techniques, excitation light, which has wavelengths falling within the excitation wavelength range for an intrinsic dye in the living body, is irradiated to a region of interest in the living body (i.e., the region which is to be used in making a diagnosis). The intrinsic dye in the living body is thus excited with the excitation light and produces fluorescence. By the detection of the fluorescence, the location and infiltration range of the diseased part is displayed as an image, and the displayed image is used in making a diagnosis of the tumor part.
Further, a different fluorescence diagnosing system has been proposed in, for example, Japanese Patent Application No. 7(1995)-252295. With the proposed fluorescence diagnosing system, instead of the two-dimensional image as described above being formed, the intensity of fluorescence produced from each of different points in a region of a living body is detected. A judgment is then made as to whether each point in the region of the living body belongs or does not belong to a tumor part.
However, the fluorescence diagnosing systems described above have the problems described below. Specifically, since a region in a living body has protrusions and recesses, the distance between the light source of the excitation light irradiating means and the region of interest in the living body is not uniform. Therefore, ordinarily, the irradiance of the excitation light at the living body portion, which is exposed to the excitation light, is non-uniform. In general, the intensity of fluorescence is approximately in proportion to the irradiance of the excitation light, and the irradiance of the excitation light at the portion, which is exposed to the excitation light, is in inverse proportion to the square of the distance between the light source of the excitation light irradiating means and the portion, which is exposed to the excitation light. Accordingly, the problems occur in that a normal part, which is located close to the light source, produces the fluorescence having a higher intensity than the intensity of the fluorescence produced by a diseased part, which is located remote from the light source. The problems also occur in that the intensity of the fluorescence from a diseased part, which is located at a position inclined with respect to the excitation light, becomes markedly low. Thus if the irradiance of the excitation light is non-uniform, the intensity of the fluorescence will vary in accordance with the level of the irradiance of the excitation light, and therefore an error will often be made in diagnosis of a tumor part.
Therefore, fluorescence diagnosing systems, which are designed such that a change in the intensity of fluorescence due to the non-uniformity of the distance with respect to the region of interest in the living body may be compensated for, have been proposed in, for example, U.S. Pat. No. 4,768,513 and Japanese Patent Publication No. 3(1991)-58729. With the fluorescence diagnosing system proposed in Japanese Patent Publication No. 3(1991)-58729, excitation light is irradiated to a portion of a living body, to which a photosensitive substance having a strong affinity for a diseased part has been administered, and the fluorescence produced by the photosensitive substance is detected. Also, the excitation light reflected from the portion of the living body is detected. An image operation is then carried out in accordance with division of the fluorescence component and the reflected excitation light component by each other. By the division, the term due to the distance with respect to the region of interest in the living body is erased. However, in the results of the division of the fluorescence component and the reflected excitation light component by each other, the term concerning the reflectivity of the portion exposed to the excitation light remains unerased. Consequently, the problems remain uneliminated in that a fluorescence image reflecting the distribution of the fluorescent diagnosis drug cannot be obtained.
A different fluorescence imaging technique is proposed in, for example, "Fluorescence Imaging of Early Lung Cancer," Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vol. 12, No. 3, 1990. With the proposed technique, intrinsic fluorescence, which is produced by an intrinsic dye in an region of interest in a living body when the region of interest is exposed to excitation light, is separated into a component of the green wavelength region (hereinbelow referred to as the "green region component G") and a component of the red wavelength region (hereinbelow referred to as the "red region component R"). An image operation is then carried out in accordance with division of the red region component R and the green region component G by each other, and the results of the division are displayed. The proposed technique utilizes the findings in that the spectrum of the intrinsic fluorescence produced by a normal part is different from the spectrum of the intrinsic fluorescence produced by a diseased part. Specifically, when the spectrum of the intrinsic fluorescence, which is produced by the intrinsic dye at a normal part in the living body, and the spectrum of the intrinsic fluorescence, which is produced by the intrinsic dye at a diseased part in the living body, are compared with each other, in particular, the intensity of the green region of the spectrum obtained from the diseased part is markedly lower than the intensity of the green region of the spectrum obtained from the normal part. Therefore, the degree of reduction in the intensity of the green region component G of the intrinsic fluorescence, which is obtained from the diseased part, as compared with the intensity of the green region component G of the intrinsic fluorescence obtained from the normal part, is markedly higher than the degree of reduction in the intensity of the red region component R of the intrinsic fluorescence, which is obtained from the diseased part, as compared with the intensity of the red region component R of the intrinsic fluorescence obtained from the normal part. Therefore, only the intrinsic fluorescence from the diseased part can be specifically extracted by the division of R/G and can be displayed as an image. With the proposed technique, the term of the fluorescence intensity depending upon the distance between the excitation light source and the region of interest in the living body and the distance between the region of interest in the living body and the fluorescence receiving means can be canceled. However, the proposed technique has the problems in that, since the intensity of the intrinsic fluorescence from the diseased part is markedly low, the signal-to-noise ratio cannot be kept high.
Accordingly, a different fluorescence diagnosing technique utilizing an red/green ratio has been proposed in "Fluorescence Image Diagnosis of Cancer Using Red/Green Ratio" by Tokyo Medical College and Hamamatsu Photonics K.K., 16th symposium of The Japanese Society of Laser Medical Science, 1995. With the proposed technique, the intensity of red fluorescence from a diseased part is amplified by using a fluorescent diagnosis drug, which is capable of accumulating at the diseased part and producing red fluorescence, and an operation of R/G is carried out. As a result, a fluorescence image can be obtained such that the intensity of fluorescence from the diseased part may be kept higher than with the aforesaid technique proposed in "Fluorescence Imaging of Early Lung Cancer."
In cases where the operation of R/G is carried out as in the two techniques described above, the term of the fluorescence intensity depending upon the distance between the excitation light source and the region of interest in the living body, which is exposed to the excitation light, and the distance between the region of interest in the living body, which is exposed to the excitation light, and the fluorescence receiving means can be ignored.
However, the intensity of the green intrinsic fluorescence component from the diseased part is markedly low. Therefore, with the two techniques described above, the problems occur in that the division by a value of zero often occurs, and an error readily occurs in making the operation.